NDNF
Protein NDNF precursor (Neuron-derived neurotrophic factor) [C4orf31] [UNQ2748/PRO6487]
Publications[править]
The decline of cell function caused by ageing directly impacts the therapeutic effects of autologous stem cell transplantation for heart repair. The aim of this study was to investigate whether overexpression of neuron-derived neurotrophic factor (NDNF) can rejuvenate the adipose-derived stem cells in the elderly and such rejuvenated stem cells can be used for cardiac repair. Human adipose-derived stem cells (hADSCs) were obtained from donors age ranged from 17 to 92 years old. The effects of age on the biological characteristics of hADSCs and the expression of ageing-related genes were investigated. The effects of transplantation of NDNF over-expression stem cells on heart repair after myocardial infarction (MI) in adult mice were investigated. The proliferation, migration, adipogenic and osteogenic differentiation of hADSCs inversely correlated with age. The mRNA and protein levels of NDNF were significantly decreased in old (>60 years old) compared to young hADSCs (<40 years old). Overexpression of NDNF in old hADSCs significantly improved their proliferation and migration capacity in vitro. Transplantation of NDNF-overexpressing old hADSCs preserved cardiac function through promoting angiogenesis on MI mice. NDNF rejuvenated the cellular function of aged hADSCs. Implantation of NDNF-rejuvenated hADSCs improved angiogenesis and cardiac function in infarcted mouse hearts.
MeSH Terms
- Adipocytes
- Adipose Tissue
- Adolescent
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Animals
- Cell Differentiation
- Cell Movement
- Cell Proliferation
- Heart
- Heart Injuries
- Humans
- Intercellular Signaling Peptides and Proteins
- Mice
- Mice, Inbred C57BL
- Middle Aged
- Myocardial Infarction
- Nerve Tissue Proteins
- Regeneration
- Rejuvenation
- Stem Cell Transplantation
- Stem Cells
- Transplantation, Heterologous
- Young Adult
Keywords
- NDNF
- ageing
- cardiac injury repair
- human adipose-derived stem cells
- rejuvenation
Reduced regenerative capacity of aged stem cells hampers the benefits of autologous cell therapy for cardiac regeneration. This study investigated whether neuron-derived neurotrophic factor (NDNF) could rejuvenate aged human bone marrow (hBM)- multipotent mesenchymal stromal cells (MSCs) and whether the rejuvenated hBM-MSCs could improve cardiac repair after ischemic injury. Over-expression of NDNF in old hBM-MSCs decreased cell senescence and apoptosis. Engraftment of NDNF over-expressing old hBM-MSCs into the ischemic area of mouse hearts resulted in improved cardiac function after myocardial infarction, while promoting implanted stem cell survival. Our findings suggest NDNF could be a new factor to rejuvenate aged stem cells and improve their capability to repair the aged heart after injury.
Keywords
- CDC, cardiosphere-derived cell
- MI, myocardial infarction
- MSC, multipotent mesenchymal stromal cell
- NDNF
- NDNF, neuron-derived neurotrophic factor
- RGN, regucalcin
- aging
- hBM, human bone marrow
- heart function
- human stem cells
- mRNA, messenger ribonucleic acid
- myocardial infarction
- p-Akt, phosphorylated Akt
- rejuvenation